Organophosphorus (OP) insecticides are widely used and constitute an appreciable exposure hazard, especially for children in rural areas because of the intense agricultural activity. OP insecticides or their metabolites are anticholinesterases, and lead to hyperexcitability in the nervous system because of the accumulation of acetylcholine. OP insecticides, have been implicated in causing behavioral effects in children, including hyperactivity. Perturbation of the cholinergic system by an OP insecticide during nervous system development may cause permanent deficits in cognition since the cholinergic system is involved in learning and memory. It is therefore possible that exposure to OP insecticides may be responsible for cognitive deficits and hyperactivity which could be manifest as reduced learning ability and attention deficit disorder/hyperactivity disorder. Our laboratories have been involved in the study of the metabolism and neurochemical sensitivity of adults and juveniles to OP insecticides. However, our laboratories have not performed behavioral studies on juveniles. Most behavioral studies existing at the present on the effects of OP compounds on juveniles have used high dosages to demonstrate effects. It is still unknown whether levels of insecticides encountered as dietary contaminants or as environmental contarninants from agricultural or domestic uses can lead to behavioral effects. The persistence of the acetylcholinesterase (AChE) inhibition, resulting in part from "aging" (permanent inactivation) of the inhibited enzyme. may also play an important role in the severity of the behavioral deficits. This project will determine whether deficits in behavior occur in juvenile rats treated neonatally with the OP insecticide chlorpyrifos, and whether these deficits correlate with the persistence (including aging) of the brain AChE inhibition. The behaviors to be studied are open field (locomotor) activity (to test mainly for hyperactivity) and a delayed alternation task (to test cognition). The results will indicate whether OP insecticides could be responsible for some of.the learning deficits and hyperactivity observed in schools today, particularly in disadvantaged populations.